On November 9, 2021 Bolt Biotherapeutics, Inc. (NASDAQ: BOLT) a clinical-stage biotechnology company pioneering a new class of immuno-oncology agents that combine the targeting precision of antibodies with the power of both the innate and adaptive immune systems, reported financial results for the third quarter ended September 30, 2021 and provided an update on recent business highlights (Press release, Bolt Biotherapeutics, NOV 9, 2021, View Source [SID1234594893]).

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"This quarter was notable for the significant progress we made across our entire pipeline of novel ISACs and with successful partnering of Bolt’s pioneering technology. We continued robust enrollment of the dose escalation portion of the BDC-1001 Phase 1/2 trial and we anticipate initiation of the combination dose escalation with Opdivo by year-end," said Randall C. Schatzman, Ph.D., Chief Executive Officer of Bolt Biotherapeutics. "We look forward to providing an update on our progress with BDC-1001 at the ESMO (Free ESMO Whitepaper) Immuno-Oncology Congress in December."

Recent Business Highlights and Anticipated Milestones

Progress in the BDC-1001 Phase 1/2 trial in HER2-expressing solid tumors, with a monotherapy interim update in Q4 2021 – Interim data from more than 50 patients treated at increasing exposure levels will be presented in December at the ESMO (Free ESMO Whitepaper) Immuno-Oncology Congress 2021. The presentation will provide further details of the continued favorable safety and tolerability profile along with insights from data on phamacokinetics, tumor and serum biomarkers and early signs of clinical activity. The positive data support continued investigation of an optimal dosing regimen and Phase 2 initiation in 2022.

R&D collaboration with Innovent Biologics to develop up to three anti-cancer ISAC candidates – In August 2021, Bolt Biotherapeutics announced an R&D collaboration to apply Innovent’s proprietary therapeutic antibody portfolio and discovery capability and Bolt’s ISAC platform technology and myeloid biology expertise with the goal of creating up to three new cancer treatments with the potential to provide significant benefit to patients. Bolt Biotherapeutics received an upfront payment of $5.0 million in cash from Innovent at signing and a possible future equity investment of up to $10.0 million, as well as milestones and royalties. Bolt Biotherapeutics retains the option to license global rights outside of Greater China for one program and North American rights for another program.

Clinical collaboration and supply agreement with Bristol Myers Squibb to investigate BDC-1001 in combination with Opdivo (nivolumab) – In September 2021, Bolt Biotherapeutics announced a clinical collaboration and supply agreement with Bristol Myers Squibb Company (BMS) to investigate BDC-1001 in combination with BMS’ PD-1 checkpoint inhibitor Opdivo. BMS will provide Opdivo for the combination dose escalation and combination dose expansion portions of the Phase 1/2 clinical trial in patients with HER2-expressing solid tumors, including breast, gastroesophageal and colorectal. The combination portion of the trial is expected to start in the fourth quarter of 2021.

IND-enabling studies with BDC-2034 (CEA-targeting ISAC) remain on track. GLP toxicology studies are expected to commence in first quarter of 2022 and IND filing in mid-2022.

Cash, cash equivalents, and marketable securities of $290.5 million as of September 30, 2021, plus the $5.0 million upfront payment received in October 2021 for the R&D collaboration with Innovent Biologics, is expected to fund operations and the advancement of the company’s product pipeline to achieve multiple key milestones through the end of 2023.
Upcoming Events

At the 2021 Society for Immunotherapy of Cancer (SITC) (Free SITC Whitepaper) Annual Meeting, company scientists will be presenting data on three proprietary, early-stage oncology pipeline programs, including two Boltbody ISAC candidates and a novel agonist antibody targeting Dectin-2 (previously known as TAM1). Information about these presentations can be found below and on the 2021 SITC (Free SITC Whitepaper) Annual Meeting website. All poster presentations will take place from 7:00 a.m. – 8:30 p.m. ET on Saturday, November 13, 2021.
William G. Mallet, Ph.D., will present a poster entitled "BDC-2034: Discovery of a CEA-targeting Immune-Stimulating Antibody Conjugate (ISAC) for Solid Tumors."
Justin A. Kenkel, Ph.D., will present a poster entitled "Dectin-2, a novel target for tumor macrophage reprogramming in cancer immunotherapy."
Marcin Kowanetz, Ph.D., will present a poster entitled "PD-L1-targeted ISAC combines myeloid cell activation, immune-checkpoint inhibition and ADCP to improve anti-tumor efficacy over anti-PD-L1 antibodies in preclinical models."
At the Stifel 2021 Virtual Healthcare Conference, management will participate in a virtual fireside chat and be available for meetings with the investment community on Tuesday, November 16, 2021.
At the ESMO (Free ESMO Whitepaper) Immuno-Oncology Congress 2021, interim results will be presented from the monotherapy dose-escalation portion of a Phase 1/2 study of BDC-1001 for the treatment of patients with advanced HER2-expressing solid tumors, including breast, gastroesophageal and colorectal cancer. ESMO (Free ESMO Whitepaper) I/O is being held in Geneva, Switzerland in person and virtually from December 8-11, 2021.

Title: Preliminary results from a phase 1/2 study of BDC-1001, a novel HER2 targeting TLR7/8 immune-stimulating antibody conjugate (ISAC), in patients (pts) with advanced HER2-expressing solid tumors
Presenter: Manish R. Sharma, M.D., Associate Director of Clinical Research, START Midwest
Presentation Number: 164P
Details: December 8-11, 2021, ePoster presentation
Third Quarter 2021 Financial Results

Cash Position – Cash, cash equivalents, and marketable securities were $290.5 million as of September 30, 2021, compared to $310.9 million as of June 30, 2021. Bolt Biotherapeutics expects this cash balance to fund operations through the end of 2023.

Collaboration Revenue – Revenue was $0.8 million for the quarter ended September 30, 2021, compared to zero for the same quarter in 2020. Revenue in 2021 was generated from services performed under the R&D collaboration with Genmab.

Research and Development Expenses – R&D expenses were $19.3 million for the quarter ended September 30, 2021, compared to $9.5 million for the same quarter in 2020, with the largest two increases due to manufacturing expenses related to BDC-1001 and BDC-2034 and personnel expenses relating to an increase in headcount.

General and Administrative (G&A) Expenses – G&A expenses were $4.9 million for the quarter ended September 30, 2021, compared to $2.9 million for the same quarter in 2020, with the largest increase due to personnel expenses relating to an increase in headcount.

Loss from Operations – Loss from operations was $23.5 million for the quarter ended September 30, 2021, compared to $12.4 million for the same quarter in 2020.

Opdivo is a trademark of Bristol-Myers Squibb Company.

On November 9, 2021 Jazz Pharmaceuticals plc (Nasdaq: JAZZ) reported that the company will virtually participate in the following upcoming investor conferences (Press release, Jazz Pharmaceuticals, NOV 9, 2021, View Source [SID1234594909]):

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Jefferies London Healthcare Conference on Tuesday, November 16, 2021

The presentation is scheduled for 11:20 – 11:55 a.m. ET / 4:20 – 4:55 p.m. GMT
Evercore ISI HealthCONx Conference on Tuesday, November 30, 2021

The presentation is scheduled for 2:40 – 3:25 p.m. ET / 7:40 – 8:25 p.m. GMT
Jazz will virtually participate in both conferences and webcasts of the presentations will be available via the Investors section of the Jazz Pharmaceuticals website at www.jazzpharma.com. Replays of the webcasts will be available on the website for 30 days.

On November 9, 2021 Vigeo Therapeutics, a clinical-stage immuno-oncology company pioneering novel cancer therapies, reported new clinical data from its Phase 1/2 expansion study evaluating the single-agent activity of VT1021 in subjects with pancreatic cancer and recurrent glioblastoma (rGBM) (Press release, Vigeo Therapeutics, NOV 9, 2021, View Source [SID1234594925]). The data is being presented in the poster session at the Society for Immunotherapy of Cancer (SITC) (Free SITC Whitepaper)’s (SITC) (Free SITC Whitepaper) 2021 Annual Meeting, taking place from November 10-14, 2021.

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Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

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VT1021 is a first-in-class compound that induces the expression of Tsp-1 in the tumor microenvironment (TME). Tsp-1 then blocks the CD47 immune checkpoint and reprograms the CD36 receptor to induce tumor cell apoptosis, inhibit angiogenesis, and reprogram macrophages from the M2 to M1 phenotype. In the completed open-label, multicenter Phase 1/2 study (NCT03364400), the safety and preliminary anti-tumor efficacy of single-agent VT1021 was evaluated in subjects enrolled in both dose escalation and dose expansion cohorts. Results of the all-comer escalation cohort were presented at SITC (Free SITC Whitepaper) in 2020. In 2021, Vigeo is presenting the results of the expansion cohorts, which focused primarily on pancreatic cancer and rGBM, as well as other indications.

In the pancreatic cancer expansion cohort, VT1021, when administered as a single agent, was able to induce a reduction in tumor volume in 38% of subjects with measurable disease. VT1021 was able to reprogram the immune reactivity of the TME as evidenced by an increase in cytotoxic T lymphocytes (CTLs) as well as in the ratio of M1:M2 macrophages. These findings suggest that VT1021, in addition to its single agent activity, could be a potent and synergistic combination with checkpoint inhibitors.

Consistent with the reprogramming of the TME, Tsp-1 expression was significantly increased by VT1021 treatment across all tumor types. Induction of Tsp-1 protein was observed in circulating PBMCs, platelets and plasma, along with mRNA levels in PBMCs. Additionally, analysis of paired biopsy samples revealed increased Tsp-1 accumulation in MDSCs in the TME. Taken together these findings validate of the biological activity of VT021 via the induction of Tsp-1 in the TME.

"We are highly encouraged by the new data being presented at SITC (Free SITC Whitepaper), which demonstrate both a favorable safety profile for VT1021 as well as early signals of efficacy in pancreatic cancer – especially for those subjects with tumors expressing high levels of both CD47 and CD36," said CEO Jim Mahoney, "Out of 14 patients, 5 patients showed reduction in tumor burden. Based on these findings, we believe that VT1021, a dual-CD47/CD36 modulating agent, has strong potential as a treatment for pancreatic cancer patients."

Vigeo plans to initiate Phase 2/3 studies in both pancreatic cancer and rGBM during the first half of 2022. Vigeo will present additional results from the GBM expansion cohort at the Society for Neuro-Oncology (SNO) Conference in November 2021 in Boston, MA.

Details for the SITC (Free SITC Whitepaper) 2021 presentations are as follows:

Title: Clinical update of VT1021, a first-in-class CD36 and CD47 targeting immunomodulating agent, in subjects with pancreatic cancer and other solid tumors stratified by novel biomarkers
Presenter: Marsha Crochiere, PhD, Director of Translational Sciences, Vigeo Therapeutics
Session: Virtual Poster Hall
Poster #: 369
Date and time: A copy of the poster will be available on-demand starting Friday, November 12th at 7:00 AM ET

Title: Development of Thrombospondin-1 as a clinical pharmacodynamic biomarker for VT1021, a first-in-class therapeutic agent that reprograms the tumor microenvironment.
Presenter: Jian Jenny Chen, PhD, Director Scientific Research and Development, Vigeo Therapeutics
Session: Virtual Poster Hall
Poster #: 375
Date and time: A copy of the poster will be available on-demand starting Friday, November 12th at 7:00 AM ET

About VT1021
Vigeo’s lead asset, VT1021, is a first-in-class dual modulating compound that blocks the CD47 immune checkpoint and activates the apoptotic and macrophage reprogramming activity of CD36. The result of the dual modulating activity is the induction of apoptosis as well as an increase in both CTL:Treg and M1:M2 macrophage ratio. The biological/therapeutic activity of VT1021 is mediated by the stimulation of thrombospondin-1 (Tsp-1). Through these dual-modulating effects VT1021 reprograms the tumor microenvironment (TME) from one that is immune suppressive, or "cold," to immune enhanced (or sensitized), or "hot," that are more susceptible to attack from the immune system. Vigeo is developing VT1021 as a therapeutic agent across a range of cancers, with a current focus on solid tumors.

On November 9, 2021 Imvax, Inc., a clinical-stage biotechnology company developing personalized, whole tumor-derived immunotherapies, reported data showing the mechanisms by which IGV-001 produces broad immune activation at the Society for Immunotherapy of Cancer (SITC) (Free SITC Whitepaper) Annual Meeting (Press release, Imvax, NOV 9, 2021, View Source [SID1234594941]). The data from in vitro and in vivo studies highlight the effects of IGV-001 on inducing both innate and adaptive immune responses to tumor cells and point to the potential mechanism behind observed clinical activity for IGV-001 in the treatment of glioblastoma.

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"These exciting mechanistic data substantiate the anti-tumor effects we’ve observed in prior clinical trials of IGV-001. The insights reported here will inform our ongoing clinical development of IGV-001 for glioblastoma, a disease in great need of effective new treatments," said John P. Furey, Chief Executive Officer. "Importantly, these studies also underscore the potential expansion of Imvax’s approach to a wide range of solid tumors and bolster our ongoing preclinical work in hepatocellular, ovarian, pancreatic, and other cancers."

For these in vitro studies, IGV-001 was prepared with patient tumor cells. It was then co-cultured with patient-derived peripheral blood mononuclear cells (PBMCs) to evaluate activated and memory T cell subsets and responses. These studies found an elevated percentage of activated potentially anti-tumor CD4 and CD8 T cells as well as increased central and effector memory phenotypes in both T cell subsets compared to IMV-001-treated PBMC controls. Tumor cells treated with Insulin-like Growth Factor-1 Receptor antisense ‘IMV-001’ also released significantly more (p<0.01) ATP than untreated or sense oligonucleotide-treated controls, suggesting immunogenic cell death.

In vivo studies were performed on C57BL/6 albino mice. Biodiffusion chambers were loaded with either IMV-001 or a saline control, plus GL261-Luc cells, irradiated and implanted into the mice’s flanks for 48 hours, similar to the combination product dosed in investigator-initiated Phase 1 studies of IGV-001 and planned for dosing in the Company’s upcoming Phase 2 clinical trial (NCT04485949). GL261-Luc intracranial tumor challenge was conducted 28 days after chamber implantation. At the termination of the study, 58 days post–intracranial tumor challenge, 59% of IGV-001-treated mice were alive and continued to gain weight, whereas all mice in the control group died by day 24 (p<0.001). Additionally, IGV-001-treated mice with lower tumor burden had less circulating IL-6 (P<0.01), pointing to a means of quantifying IGV-001’s suppression of tumor growth. Finally, Elispot assays demonstrated that mice treated with IGV-001 showed enhanced T cell IFNγ responses to tumor cell antigens, compared to controls.

On November 9, 2021 Horizon Therapeutics plc (Nasdaq: HZNP) reported that the Company will participate in the following upcoming conferences (Press release, Horizon Therapeutics, NOV 9, 2021, View Source [SID1234594957]):

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Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

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Guggenheim 3rd Annual Neuro/Immunology Conference (Virtual)

Date: Monday, Nov. 15, 2021
Presentation Time: 9 a.m. ET
Stifel 2021 Health Care Conference (Virtual)

Date: Tuesday, Nov. 16, 2021
Presentation Time: 2 p.m. ET
Piper Sandler 33rd Annual Health Care Conference (Virtual)

Date: Tuesday, Nov. 30, 2021
Presentation Time: 9 a.m. ET
These conference presentations will be webcast live and may be accessed by visiting Horizon’s website at View Source A replay of the webcasts will be available following the events.